ENTINOSTAT

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H20N4O3
Molecular Weight	376.4085
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=CC=CC=C1NC(=O)C2=CC=C(CNC(=O)OCC3=CN=CC=C3)C=C2

InChI

InChIKey=INVTYAOGFAGBOE-UHFFFAOYSA-N

InChI=1S/C21H20N4O3/c22-18-5-1-2-6-19(18)25-20(26)17-9-7-15(8-10-17)13-24-21(27)28-14-16-4-3-11-23-12-16/h1-12H,13-14,22H2,(H,24,27)(H,25,26)

HIDE SMILES / InChI

Molecular Formula	C21H20N4O3
Molecular Weight	376.4085
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://adisinsight.springer.com/drugs/800012663
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17383217 https://www.ncbi.nlm.nih.gov/pubmed/21888556 https://www.ncbi.nlm.nih.gov/pubmed/12975486

Entinostat (MS-275) is an orally active, highly selective, small-molecule histone deacetylase inhibitor (HDACi) derived from benzamide. Entinostat preferentially inhibited HDAC1 versus HDAC3 and had no inhibitory activity toward HDAC8. The time to maximum plasma concentration (tmax) of entinostat ranged from 0.5 to 60h (median of 2h). Elimination of the drug was bi-exponential, with a terminal half-life of 30-80h. Entinostat is a well-tolerated that demonstrates promising therapeutic potential in both solid and hematologic malignancies. Its efficacy does not appear directly dose-related, and as such, more relevant biomarkers are needed to adequately assess its activity.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histone deacetylase 1 51 Target ID: CHEMBL325 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12975486	Inhibitor 8504		0.3 µM [IC50]
Histone deacetylase 3 35 Target ID: CHEMBL1829 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12975486	Inhibitor 8504		8.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Breast cancer 432 Sources: http://adisinsight.springer.com/drugs/800012663	Primary	Phase III 665	Unknown Approved Use Unknown
Non-small cell lung cancer 211 Sources: http://adisinsight.springer.com/drugs/800012663	Primary	Phase II 1147	Unknown Approved Use Unknown
Acute myeloid leukemia 141 Sources: http://adisinsight.springer.com/drugs/800012663	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
45.1 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/28326839/	10 mg/kg 1 times / 2 weeks multiple, oral dose: 10 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered:		ENTINOSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
114.3 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22134508	4 mg/m² 1 times / week multiple, oral dose: 4 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: Isotretinoin	Isotretinoin	ENTINOSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
529 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/28326839/	10 mg/kg 1 times / 2 weeks multiple, oral dose: 10 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered:		ENTINOSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
586.6 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22134508	4 mg/m² 1 times / week multiple, oral dose: 4 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: Isotretinoin	Isotretinoin	ENTINOSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
51.6 h REVIEW https://pubmed.ncbi.nlm.nih.gov/28326839/	10 mg/kg 1 times / 2 weeks multiple, oral dose: 10 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered:		ENTINOSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
129.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22134508	4 mg/m² 1 times / week multiple, oral dose: 4 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: Isotretinoin	Isotretinoin	ENTINOSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
18.8% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16028097/	10 mg/m² single, oral dose: 10 mg/m² route of administration: Oral experiment type: SINGLE co-administered:		ENTINOSTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252			inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYPs 29 P-gp 1741	OATP1B3 435 UGTs 13 OATP1B1 503 CYPs 33	BCRP 101 CYP19 1

Drug as perpetrator

Target	Modality	Activity
BCRP 985	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/26133921/	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/609494#sid=103197084	yes [IC50 0.73 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363676644 \| https://pubmed.ncbi.nlm.nih.gov/29979729/	yes [IC50 9.2 uM]
CYP19 2	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/21245100/	yes
CYPs 35	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28326839/	yes

Drug as victim

Target	Modality	Activity
CYPs 33	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16583304/	no
OATP1B1 503	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16583304/	no
OATP1B3 435	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16583304/	no
UGTs 13	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16583304/	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/21742496/ \| https://pubmed.ncbi.nlm.nih.gov/21650221/

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P002KUN	https://www.1pchem.com/search?query=1P002KUN
A2B Chem	AB19535	http://a2bchem.com/prod/AB19535
AChemBlock	M15388	http://www.achemblock.com/catalogsearch/result/?q=M15388
Achemo Scientific Limited	AC-66533	http://www.achemo.com/search/?Keyword=AC-66533
AK Scientific	V2451	https://aksci.com/item_detail.php?cat=V2451
Ambeed	A122285	http://www.ambeed.com/search/Search.html?keyword=A122285
AOBIOUS INC	AOB2570	http://aobious.com/aobious/search?search_query=AOB2570
ApexBio Technology	A8171	https://www.apexbt.com/catalogsearch/result/?q=A8171
AstaTech	41168	http://astatechinc.com/CPSResult.php?CRNO=41168
Axon MedChem	1803	https://www.axonmedchem.com/product/1803
BioSynth	W-201831	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/W-201831
BOC Sciences	209783-80-2	http://www.bocsci.com/description.asp?cas=209783-80-2
Capot Chemical	24433	https://www.capotchem.com/search.do?q=24433
Cayman Chemical	13284	http://www.caymanchem.com/app/template/Product.vm/catalog/13284
Chem Scene	CS-0511	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0511
ChemShuttle	140489	https://www.chemshuttle.com/catalogsearch/result/?q=140489
ChemShuttle	149125	https://www.chemshuttle.com/catalogsearch/result/?q=149125
eMolecules	222573108	https://orderbb.emolecules.com/search/#?query=222573108
eMolecules	252359243	https://orderbb.emolecules.com/search/#?query=252359243
eMolecules	31239709	https://orderbb.emolecules.com/search/#?query=31239709
Enamine	EN300-6488260	https://www.enaminestore.com/catalog/EN300-6488260
eNovation Chemicals	D395222	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D395222&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	D586663	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D586663&searchbtn.x=0&searchbtn.y=0
Excenen	EX-A038	http://www.excenen.com/searchresultlist.php?id=EX-A038
Exclusive Chemistry	2117	http://www.exchemistry.com/chem-catalog/product-2117.html
Fluorochem	50699	http://www.fluorochem.co.uk/Products/Product?code=050699
Hairui	ENJL011	http://www.hairuichem.com/en/product/search.do?q=ENJL011
KeyOrganics	AS-17906	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17906
Lab Network	LN01285798	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01285798
mcule	MCULE-6200347297	https://mcule.com/MCULE-6200347297/
mcule	MCULE-9534048478	https://mcule.com/MCULE-9534048478/
MedChem Express	HY-12163	https://www.medchemexpress.com/search.html?q=HY-12163&ft=&fa=&fp=
Molnova	M13310	https://www.molnova.com/en/serch-list.html?keywords=M13310
MolPort	MolPort-005-942-713	https://www.molport.com/shop/molecule-link/MolPort-005-942-713
MuseChem	I002611	https://www.musechem.com/product/I002611.html
PI Chemicals	PI-38652	http://www.pipharm.com/catalog_products/PI-38652.html
Selleck Chemicals	S1053	http://www.selleckchem.com/search.html?searchDTO.searchParam=S1053
ShangHai Biochempartner	BCP000127	http://www.biochempartner.com/search_BCP000127
ShangHai Biochempartner	BCP01824	http://www.biochempartner.com/search_BCP01824
TargetMol	T6233	https://www.targetmol.com/search?keyword=T6233
Toronto Research Chemicals	E559300	https://www.trc-canada.com/product-detail/?CatNum=E559300
W&J PharmaChem	RT-	http://wjpharmachem.com/new/searcht.php?keyword=RT-

PubMed

Title	Date	PubMed
Enhanced radiation-induced cell killing and prolongation of gammaH2AX foci expression by the histone deacetylase inhibitor MS-275.	2004 Jan 1	14729640
Enhancement of xenograft tumor radiosensitivity by the histone deacetylase inhibitor MS-275 and correlation with histone hyperacetylation.	2004 Sep 15	15447991
In vivo imaging of retinoic acid receptor beta2 transcriptional activation by the histone deacetylase inhibitor MS-275 in retinoid-resistant prostate cancer cells.	2005 Jun 15	15651062
Ex vivo therapy of malignant melanomas transplanted into organotypic brain slice cultures using inhibitors of histone deacetylases.	2006 Aug	16773328
The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells.	2007 Mar	17186014
MAGE-A9 mRNA and protein expression in bladder cancer.	2007 May 15	17290406
Histone deacetylase inhibitors induce cell death and enhance the apoptosis-inducing activity of TRAIL in Ewing's sarcoma cells.	2007 Nov	17486365
Antiproliferative activities of a library of hybrids between indanones and HDAC inhibitor SAHA and MS-275 analogues.	2007 Nov 15	17897824
Phase I trial of MS-275, a histone deacetylase inhibitor, administered weekly in refractory solid tumors and lymphoid malignancies.	2007 Sep 15	17875771
Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells.	2007 Sep 7	17724801
Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors.	2008 Jan 15	17868033
Histone deacetylase inhibitors in lymphoma and solid malignancies.	2008 Mar	18366289
Improved synthesis of histone deacetylase inhibitors (HDIs) (MS-275 and CI-994) and inhibitory effects of HDIs alone or in combination with RAMBAs or retinoids on growth of human LNCaP prostate cancer cells and tumor xenografts.	2008 Mar 15	18166465
Potentiation of reactive oxygen species is a marker for synergistic cytotoxicity of MS-275 and 5-azacytidine in leukemic cells.	2008 May	18031811
Determination of a benzamide histone deacetylase inhibitor, MS-275, in human plasma by liquid chromatography with mass-spectrometric detection.	2009 Jan 15	19117815
Reactivation of death receptor 4 (DR4) expression sensitizes medulloblastoma cell lines to TRAIL.	2009 Jul	19148581
Epigenetic modifiers: basic understanding and clinical development.	2009 Jun 15	19509169
Rescue of major histocompatibility-DR surface expression in retinoblastoma-defective, non-small cell lung carcinoma cells by the MS-275 histone deacetylase inhibitor.	2009 Mar	19252299
Epigenetic modulation of mGlu2 receptors by histone deacetylase inhibitors in the treatment of inflammatory pain.	2009 May	19255242
HDAC inhibitor SNDX-275 induces apoptosis in erbB2-overexpressing breast cancer cells via down-regulation of erbB3 expression.	2009 Nov 1	19826038
Epigenetic influences on sensory regeneration: histone deacetylases regulate supporting cell proliferation in the avian utricle.	2009 Sep	19340485
Antidepressant actions of histone deacetylase inhibitors.	2009 Sep 16	19759294
MS275 enhances cytotoxicity induced by 5-fluorouracil in the colorectal cancer cells.	2010 Feb 10	19853597
Experimental study on inhibitory effects of histone deacetylase inhibitor MS-275 and TSA on bladder cancer cells.	2010 Nov-Dec	19181544

Patents

Sample Use Guides

In Vivo Use Guide

Phase I trial data have shown that daily dosing of entinostat is not tolerated. Administration of the drug every 2 weeks or weekly at doses of ≤10 mg/m2 was much better tolerated than daily dosing. The recommended phase II dose for entinostat is 4 mg/ m2 once weekly (solid tumors).

Route of Administration: Oral

In Vitro Use Guide

Entinostat (MS-275) exerts dose-dependent effects in human leukemia cells, i.e., p21(CIP1/WAF1)-dependent growth arrest and differentiation at low drug concentrations (e.g., 1 uM) and a marked induction of ROS, mitochondrial damage, caspase activation, and apoptosis at higher concentrations (e.g., 5 uM).

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:15:14 GMT 2025` Edited by `admin` on `Mon Mar 31 18:15:14 GMT 2025`
Record UNII	1ZNY4FKK9H
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ENTINOSTAT

Official Name

English

MS-27-275

Preferred Name

English

Entinostat [WHO-DD]

Common Name

English

ENTINOSTAT [USAN]

Common Name

English

Pyridin-3-ylmethyl ({4-[(2-aminophenyl)carbamoyl]phenyl}methyl)carbamate

Systematic Name

English

CARBAMIC ACID, N-((4-(((2-AMINOPHENYL)AMINO)CARBONYL)PHENYL)METHYL)-, 3- PYRIDINYLMETHYL ESTER

Common Name

English

entinostat [INN]

Common Name

English

MS-275-27

Code

English

ENTINOSTAT [JAN]

Common Name

English

SNDX-275

Code

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/10/732